Gabapentin Prophylaxis of Clozapine-Induced Seizures

Aaron, a 15-year-old boy, was seen for treatment of childhood-onset schizophrenia that had been refractory to pharmacotherapy with mesoridazine, thioridazine, fluphenazine, and haloperidol. There was no personal or family history of seizures. After a medication washout, Aaron began treatment with clozapine. After 4 weeks, when his dose had reached 400 mg/day and he was showing signs of improvement, right-sided myoclonic jerks (multiple, involuntary right arm and shoulder movements with the appearance of punching the air) were noted.

The next day Aaron experienced a 3-minute tonic-clonic seizure followed by a period of postictal confusion. An EEG showed bihemispheric epileptiform activity. His clozapine dose was halved, and treatment with phenytoin was initiated. The development of eosinophilia and an erythematous rash on the dorsum of his hands after 2 days curtailed this treatment; thrombocytopenia curtailed treatment with valproic acid. Clozapine was eventually discontinued after 2 months at a very low dose (25 mg/day) because of continued epileptiform activity on Aaron’s EEGs despite treatment with phenobarbital.

At age 19, despite treatment with risperidone (4 mg/day), a high dose of olanzapine (60 mg/day), and augmentation with haloperidol (2 mg/day), Aaron remained severely disabled by positive and negative symptoms and was admitted for treatment with clozapine. Although he had been taking clonazepam (2 mg/day) for 2 years for anxiety and behavioral disturbances, additional antiepileptic prophylaxis was felt to be essential, given his previous seizure.

Gabapentin was considered the most appropriate anticonvulsant for Allen after consideration of its benign side effect profile, its lack of significant drug interactions (2), and his previous adverse reactions to other anticonvulsants. Gabapentin treatment was begun, Aaron’s olanzapine dose was tapered, and clozapine treatment was slowly reintroduced. After 2 months, Aaron was discharged while receiving 2100 mg/day of gabapentin, 300 mg/day of clozapine, 25 mg/day of olanzapine, and 2 mg/day of clonazepam. After 3 months of clozapine therapy, Aaron showed significant improvement, and there was no evidence of recurrent seizure activity, either clinically or on EEGs.